Throughout this application, various publications are referenced by a number in brackets. Full citations for these publications may be found listed by number at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
Gemfibrozil (GFZ) is a compound that has been utilized as a drug for increasing intracellular accumulation of hydrophilic anionic agents (U.S. Pat. No. 5,422,372, issued Jun. 6, 1995) and as a lipid regulating composition (U.S. Pat. No. 4,859,703, issued Aug. 22, 1989). Gemfibrozil has been shown to be effective in increasing the amount of cholesterol excreted in to bile. (Ottmar Leiss et al., Metabolism, 34(1):74-82 (1985)). Gemfibrozil is described in U.S. Pat. No. 3,674,836 and in The Merck Index, 11 ed., Merck and Co., Inc. Rahway, N.J. 1989; #4280. Gemfibrozil, a drug which therapeutically lowers triglycerides and raises HDL-cholesterol levels, previously has not been reported to have antimicrobial activity. (Brown, 1987; Oliver et al., 1978 and Palmer et al., 1978).
The present invention provides for a method of inhibiting activity of an enoyl reductase enzyme in a cell which comprises contacting the cell with a compound having the structure: 
wherein each of R1, R2, R3, R4, R5 and R6 is independently selected from the group consisting of: xe2x80x94H, xe2x80x94F, xe2x80x94Cl, xe2x80x94Br, xe2x80x94I, xe2x80x94OH, xe2x80x94OR7, xe2x80x94CN, xe2x80x94COR7, xe2x80x94SR7, xe2x80x94N(R7)2, xe2x80x94NR; xe2x80x94COR8, xe2x80x94NO2, xe2x80x94(CH2)pxe2x80x94OR7, xe2x80x94COSR7, xe2x80x94COOH, xe2x80x94CONH2, xe2x80x94NH2, a straight chain or branched, substituted or unsubstituted C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, thioalkyl, methylene thioalkyl, acyl, phenyl, substituted phenyl, or heteroaryl;
wherein L is alternatively xe2x80x94Nxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94Cxe2x80x94 or xe2x80x94Cxe2x80x94;
wherein R7 is independently selected from the group consisting of xe2x80x94H, xe2x80x94F, xe2x80x94Cl, xe2x80x94Br, xe2x80x94I, xe2x80x94OH, xe2x80x94CN, xe2x80x94COH, xe2x80x94SH2, xe2x80x94NH2, xe2x80x94NHCOH, xe2x80x94(CH2)pOH, a straight chain or branched, substituted or unsubstituted C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, thioalkyl, methylene thioalkyl, acyl, phenyl, substituted phenyl, or heteroaryl;
wherein A is selected from the group consisting of xe2x80x94N2xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Cxe2x95x90Cxe2x95x90CH2xe2x80x94, xe2x80x94Cxe2x89xa1Cxe2x80x94C2HOHxe2x80x94, xe2x80x94Cxe2x89xa1Cxe2x80x94CH2xe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94Oxe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S (xe2x95x90O)2xe2x80x94, xe2x80x94Cxe2x95x90Oxe2x80x94, xe2x80x94Cxe2x95x90Oxe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94Cxe2x95x90Oxe2x80x94, xe2x80x94Cxe2x95x90Oxe2x80x94NHxe2x80x94;
wherein Q is independently an integer from 1 to 10, or if Q is 1, A may be a (C1-C10)-alkyl chain, (C1-C10)-alkenyl chain or (C1-C10)-alkynyl chain which is branched or unbranched, substituted or unsubstituted and is optionally interrupted 1 to 3 times by xe2x80x94Oxe2x80x94 or xe2x80x94Sxe2x80x94 or xe2x80x94Nxe2x80x94;
wherein X is xe2x80x94CO2xe2x80x94, xe2x80x94CHxe2x95x90CH3, phenyl, substituted phenyl, or heteroaryl, xe2x80x94O-phenyl(CH3)2, xe2x80x94C(CH2)2xe2x80x94COxe2x80x94NH2, xe2x80x94C(CH2)2xe2x80x94COOH;
or a pharmaceutically acceptable salt or ester thereof, which compound is present in a concentration effective to inhibit activity of the enzyme.